Tumour necrosis factor (TNF-alpha) in leishmaniasis. II. TNF-alpha-induced macrophage leishmanicidal activity is mediated by nitric oxide from L-arginine.
Peritoneal macrophages from CBA mice incubated with recombinant murine tumour necrosis factor (TNF-alpha) are effective in killing the protozoa parasite Leishmania major in vitro. The leishmanicidal activity is directly correlated with the level of nitrite (NO2-) in the culture supernatants. The killing of intracellular parasites can be completely inhibited by L-NG-monomethyl arginine (L-NMMA), a specific inhibitor of the L-arginine:nitric oxide (NO) pathway. The level of NO2-, which is also a measurement of NO production, in the culture supernatant of TNF-alpha-activated macrophages can be progressively decreased to basal level with increasing concentrations of L-NMMA, but not with its D-enantiomer, D-NMMA. These data demonstrate that NO is an important effector mechanism in the TNF-alpha-induced macrophage killing of intracellular protozoa.
Liew
F Y
FY
Department of Experimental Immunobiology, Wellcome Research Laboratories, Beckenham, Kent, U.K.
Li
Y
Y
Millott
S
S
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D007895:Leishmania tropica; D007896:Leishmaniasis / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008808:Mice, Inbred CBA; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D019323:omega-N-Methylarginine
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine